Many diseases affect kidney function by attacking the glomeruli, the tiny units within the kidney where blood is cleaned. Glomerular diseases include many conditions with a variety of genetic and environmental causes, but they fall into two major categories:
1. Glomerulonephritis describes the inflammation of the membrane tissue in the kidney that serves as a filter, separating wastes and extra fluid from the blood.
2. Glomerulosclerosis describes the scarring or hardening of the tiny blood vessels within the kidney.
Although glomerulonephritis and glomerulosclerosis have different causes, they can both lead to kidney failure.
Glomerular diseases damage the glomeruli, letting protein and sometimes red blood cells leak into the urine. Sometimes a glomerular disease also interferes with the clearance of waste products by the kidney, so they begin to build up in the blood. Furthermore, loss of blood proteins like albumin into the urine can result in a fall in their level in the bloodstream. In normal blood, albumin acts like a sponge, drawing extra fluid from the body into the bloodstream, where it remains until the kidneys remove it. But when albumin leaks into the urine, the blood loses its capacity to absorb extra fluid from the body. Fluid can accumulate outside the circulatory system in the face, hands, feet, or ankles and cause swelling. A number of different specific glomerular diseases are discussed below:
Mesangial proliferative glomerulonephritis is a kidney disorder characterized by swelling and blood in the urine (dark urine). It is caused by inflammation of an internal kidney structure (glomerulus), and specifically an increase in number of certain glomerular cells (mesangial cells), accompanied by antibody deposits in the mesangium layer of the glomerular capillary.
Mesangial proliferative glomerulonephritis is a form of glomerulonephritis (inflammation of the kidney glomeruli). The mesangial cells (part of the glomerular capillaries) increase in size and number, giving the glomeruli a lumpy appearance.
The mechanism that triggers the disorder is unknown, but it is believed to be some type of immune response, because inflammation of the glomeruli is associated with deposits of antibodies.
This is a relatively uncommon disorder. The term mesangial proliferative glomerulonephritis is actually a description of the microscopic pattern of this disease.
It may be seen more commonly in lupus patients who develop glomerulonephritis, and in patients who have IgA mediated kidney disease. It can affect both adults and children. Men may be affected slightly more often than women.
The disorder usually causes nephrotic syndrome (protein loss in the urine and swelling of the body). It may be present as acute, chronic, or rapidly progressive glomerulonephritis, and may progress to chronic kidney failure. Rapidly progressive glomerulonephritis (also known as crescentic glomerulonephritis) is a form of kidney disease that causes damage to the small structures (glomeruli) inside the kidneys that help filter waste and fluids from blood to form urine. The disease leads to a rapid loss of kidney function.
Collapsing glomerulopathy is a proliferative disease defined by segmental or global wrinkling of the glomerular basement membranes associated with podocyte proliferation. These lesions are particularly poor responders to standard therapies. First described as an idiopathic disorder or following HIV infection, it is now associated with a broad group of diseases and different pathogenetic mechanisms, which participate in podocyte injury and mitogenic stimulation. Because of this etiologic heterogeneity, there is clear need for new therapeutic approaches to target each variant of this entity.
Proliferative lupus nephritis is the name given to a kidney disease caused by systemic lupus erythematosus, and it occurs when autoantibodies form or are deposited in the glomeruli, causing inflammation. Ultimately, the inflammation may create scars that keep the kidneys from functioning properly.
Conventional treatment for lupus nephritis includes a combination of two drugs, cyclophosphamide, a cytotoxic agent that suppresses the immune system, and prednisolone, a corticosteroid used to reduce inflammation. A newer immunosuppressant, mychophenolate mofetil (MMF), has been used instead of cyclophosphamide. Preliminary studies indicate that MMF may be as effective as cyclophosphamide and has milder side effects.
Membranous nephropathy, also called membranous glomerulopathy, is the second most common cause of the nephrotic syndrome (proteinuria, edema, high cholesterol) in U.S. adults after diabetic nephropathy. Diagnosis of membranous nephropathy requires a kidney biopsy, which reveals unusual deposits of immunoglobulin G and complement C3, substances created by the body's immune system. Fully 75 percent of cases are idiopathic, which means that the cause of the disease is unknown. The remaining 25 percent of cases are the result of other diseases such as systemic lupus erythematosus, hepatitis B or C infection, or some forms of cancer. Drug therapies involving penicillamine, gold, or captopril have also been associated with membranous nephropathy. About 20 to 40 percent of patients with membranous nephropathy progress, usually over decades, to total kidney failure, but most patients experience either complete remission or continued symptoms without progressive kidney failure. Doctors disagree about how aggressively to treat this condition, since about 20 percent of patients recover without treatment. ACE inhibitors and ARBs are generally used to reduce proteinuria. Additional medication to control high blood pressure and edema is frequently required. Some patients benefit from steroids, but this treatment does not work for everyone. Additional immunosuppressive medications are helpful for some patients with progressive disease.
There is a need for agents and methods for preventing the onset of, or slowing the progression of glomerular diseases, such as the ones described above.